Cannabinoids regulate an insula circuit controlling water intake

Abstract

The insular cortex, or insula, is a large brain region involved in the detection of thirst and the control of water intake. However our understanding of the topographical, circuit and molecular mechanisms the controlling water intake within the insula remains parcellated. We found that type-1 cannabinoid receptors (CB1) within the insular cortex participate to the regulation of water intake, and deconstructed circuit mechanisms of this control. Topographically, we revealed that the activity of excitatory neurons in both anterior (aIC) and posterior (pIC) insula increases in response to water intake, yet removal of CB1 receptors only in the pIC decreases water intake. Interestingly, we found that CB1 receptors are highly expressed in insula projections to the basolateral amygdala (BLA), while undetectable in the neighboring central part of the amygdala. Thus, we imaged the neurons of the anterior or posterior insula targeting the BLA (aIC BLA and pIC-BLA), and found they oppositely respond to water intake, respectively decreasing and increasing their activity upon water drinking. Consistently, chemogenetic activation of pIC-BLA neurons decreased water intake. Finally, we uncovered CB1-dependent short term synaptic plasticity (depolarization-induced suppression of excitation, DSE) selectively in pIC-BLA, compared to aIC-BLA synapses. Altogether, our results support a model where CB1 signaling in the pIC-BLA pathway exerts a positive control on water intake.

Intrinsic Excitability in Layer IV–VI Anterior Insula to Basolateral Amygdala Projection Neurons Correlates with the Confidence of Taste Valence Encoding

“…However, this is rarely the case when it comes to physiological hydration or satiety inputs and the aIC, that has is primarily involved in interoceptive processes in the context food poisoning or CTA ( Chen et al, 2020 ; Y. Wu et al, 2020 ). As other studies currently in press demonstrate, hydration correlates and requires decreased activity in aIC-BLA and increases in pIC-BLA CB1 receptor-expressing neurons ( Zhao et al, 2022 ). In fact, and in further accord with our previous findings ( Lavi et al, 2018 ; Kayyal et al, 2019 ), optogenetic activation of the aIC-BLA projection was found to be anxiogenic, while physiological conditions that are associated with negative valence and anxiety were encoded by changes in activity on the projection ( Nicolas et al, 2022 ).…”

INGEsT: An Open-Source Behavioral Setup for Studying Self-motivated Ingestive Behavior and Learned Operant Behavior

“…Subsequently, internal body state information reaches cortical regions through the thalamus. The insular cortex (or insula) and medial prefrontal cortex (mPFC) are reported as key interoceptive brain areas to sense internal body states and generate proper behaviors (Craig, 2003; Livneh and Andermann, 2021; Zhao et al, 2022; Zhao et al, 2020). In vivo imaging in the insula and electrophysiological recording in the mPFC showed specific feeding-response and drinking-response neurons (Eiselt et al, 2021; Livneh et al, 2017; Livneh et al, 2020).…”